crossing96/oncoscreening huggingface dataset:
Impact of Molecular Androgen and Estrogen Response Scores on Outcomes Following Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer.	PURPOSE: Androgen and estrogen influence bladder cancer pathogenesis, but their role in modulating treatment response, especially immunotherapy, remains unclear. This post hoc analysis of the PURE-01 trial evaluated the impact of androgen and estrogen signatures on outcomes in patients with muscle-invasive bladder carcinoma treated with neoadjuvant pembrolizumab followed by radical cystectomy. EXPERIMENTAL DESIGN: Pretreatment transurethral resection of bladder tumor samples from 102 PURE-01 patients was analyzed using the Decipher Bladder whole-transcriptome assay to classify genomic subtypes. Hallmark androgen response (ARS), early estrogen response (ERS-early), and late estrogen response (ERS-late) scores were derived and visualized with boxplots. Subgroup differences were assessed using Mann-Whitney U, χ2, and Kruskal-Wallis tests. Event-free survival (EFS) was the primary endpoint, whereas pathologic response was the secondary endpoint. Cox proportional hazard models and Kaplan-Meier analyses evaluated the association of molecular scores with outcomes. Immune190 and FGFR3 signatures were also analyzed to explore their interactions with ARS and ERS. RESULTS: Luminal subtypes had the highest ARS and ERS scores across molecular classifications. Negative correlations were observed between Immune190 scores and ERS and ARS scores. ERS-late scores were highest in nonresponders and significantly associated with worse EFS. Conversely, ARS was not significantly linked to EFS. FGFR3 signature positively correlated with ARS and ERS and negatively with Immune190 scores. CONCLUSIONS: The strong association of ERS-late scores with both pathologic response and EFS suggests that this signature could guide patient stratification and treatment selection. These findings support future trials combining immunotherapy with antiestrogens in both neoadjuvant and advanced urothelial carcinoma settings.	bladder
Broadband Collision-Induced Dissociation Mass Spectrometry Imaging.	This study demonstrates the first application of broadband collision-induced dissociation (bbCID) to mass spectrometry imaging (MSI) for the identification of untargeted metabolites in human tissues. The methodology integrates bbCID with laser ablation-remote atmospheric pressure photoionization/chemical ionization (LARAPPI/CI), enabling the simultaneous acquisition of precursor and fragment ion distributions during MSI for many compounds simultaneously. In this approach, an infrared (IR) laser is used to ablate biological material, which is then ionized in the gas phase by a combination of photoionization and chemical ionization at atmospheric pressure. The method was validated using reference compounds, including thymidine and commonly used synthetic dyes, to assess ionization efficiency, fragmentation behavior, and spatial colocalization of precursor and fragment ions. Subsequently, bbCID-MSI was applied to clinical tissue samples of human bladder and kidney cancer. For the bladder cancer tissue, higher intensities of heptadecanoic acid, docosahexaenoic acid (FA(22:6)), docosapentaenoic acid (FA(22:5)), and FA(16:0) were observed in tumor regions, whereas proline was more abundant in adjacent nontumorous area. In renal cell carcinoma, cancerous regions exhibited elevated levels of polyunsaturated fatty acids such as arachidonic acid (FA(20:4)) and adrenic acid (FA(22:4)), while creatine and serine were enriched in healthy tissue zones. These findings highlight the utility of bbCID-MSI for spatially resolved metabolite analysis and its potential to reveal biologically relevant metabolic alterations associated with cancer.	bladder
Performance of the Oncuria-Detect bladder cancer test for evaluating patients presenting with haematuria: results from a real-world clinical setting.	BACKGROUND: Bladder cancer is the 9th most diagnosed cancer worldwide with high incidences reported in Europe and the United States. Here, we evaluated the real-world performance of a commercially available multiplex immunoassay (Oncuria-Detect, Nonagen Bioscience Corp, Los Angeles, CA, USA) that detects bladder cancer by simultaneously measuring a panel of 10 protein biomarkers in naturally voided urine samples. METHODS: We tested prospectively collected urine samples from a real-world cohort of 931 patients presenting to five US centres, one European centre and one Japanese centre with haematuria, in addition to 69 patients with either kidney or prostate cancer (disease controls). The algorithm training/refinement set comprised 617 subjects and the test set included 383 subjects. Assay results were collated with patient clinical data and a cancer diagnosis was defined by biopsy and pathology. The prevalence of bladder cancer in the study was 20%. RESULTS: In the training set, the Oncuria-Detect assay correctly identified bladder cancer in 105 of 121 cases. In the test set, the Oncuria-Detect assay correctly identified bladder cancer in 62 of 73 cases resulting in a sensitivity of 85%, a specificity of 72%, and a negative predictive value (NPV) of 95%. The performance of Oncuria was similar for both low-grade/low-stage and high-grade/high-stage. CONCLUSIONS: The multiplex Oncuria assay identified bladder cancer with high sensitivity and NPV. Oncuria's high NPV could effectively rule out 66% of patients from requiring subsequent cystoscopy.	bladder
Pathway-based cancer transcriptome deciphers a high-resolution intrinsic heterogeneity within bladder cancer classification.	"BACKGROUND: The heterogeneity of bladder cancer (BLCA) is affected by its inherent transcriptional properties and tumor microenvironment (TME). Stromal transcriptional components in the TME significantly influence the transcriptional classification of BLCA, and the intrinsic biological transcriptional characteristics of cancer cells may be obscured by the dominant, lineage-dependent transcriptional components of stromal origin. This study aimed to explore the degree and mechanisms by which cancer-intrinsic gene expression profiles contribute to the classification and prognosis of BLCA patients. MATERIALS AND METHODS: In this study, BLCA single-cell transcriptome data from GSE135337 were used to identify pure tumor cells in BLCA and explore the different intrinsic heterogeneous cell subgroups of BLCA through pathway-based cancer transcriptome classification. Additionally, BLCA intrinsic subtypes were uncovered in the TCGA BLCA dataset based on the characteristic genes of the subgroups. Lastly, various machine learning algorithms were applied to identify novel potential targets of BLCA, following which their pro-tumorigenic effects were experimentally verified. RESULTS: Four BLCA intrinsic subtypes with different molecular, functional and phenotypic characteristics were successfully identified. Specifically, MA and DP subtypes demonstrated malignant phenotypes, accompanied by unfavorable clinical prognoses, limited involvement in cell death pathways, marked cell proliferation, and diminished immune activation. Notably, MA subtype exhibited the most favorable response to immunotherapy, potentially attributable to its distinctive tumor immune microenvironment. DSM subtype represented an immune-rich subtype with the optimal prognosis, characterized by abundant immune cells, high levels of co-stimulatory, co-inhibitory, major histocompatibility complex molecules, and a potential for immunotherapy response. On the other hand, HM subtype was associated with a high level of autophagy and necrosis and an ""immune-hot"" TIME. Furthermore, BLCA intrinsic subtypes effectively classified independent sets of BLCAs, with limited overlap with existing transcriptional classifications and showcasing unprecedented predictive and prognostic value. Finally, the DP subtype, associated with the worst prognosis, was further analyzed, leading to the identification of three potential target genes (DAD1, CYP1B1, and REXO2) significantly associated with metabolic disorders, as well as BLCA stage and grade. CONCLUSION: This study identified a promising platform for understanding intrinsic tumor heterogeneity, which could offer new insights into the intricate molecular mechanisms of BLCA. Targeted therapy against BEXO2 may improve the prognosis of BLCA patients by regulating mitochondria-related metabolic disorders."	bladder
Neoadjuvant Radiotherapy Combined with Transurethral Photoselective Vaporization of Bladder Tumors and Postoperative Adjuvant Radiotherapy and Chemotherapy for T3 Muscle-Invasive Bladder Cancer: A Retrospective Case Series Study.	"Objective: To evaluate the efficacy and safety of neoadjuvant radiotherapy combined with transurethral photoselective vaporization of bladder tumors (PVBT), followed by postoperative adjuvant radiotherapy and chemotherapy, in the treatment of T3 muscle-invasive bladder cancer (MIBC). Background: Transurethral resection of bladder tumors combined with radiotherapy and chemotherapy, also known as trimodal therapy (TMT), is the recommended bladder-preserving approach for MIBC and has demonstrated favorable outcomes in T2 MIBC. However, T3 MIBC remains a challenging candidate for TMT due to its relatively poor prognosis. Therefore, optimizing the ""triple therapy"" strategy for T3 MIBC is essential. Methods: This was a retrospective case series. Patients with T3 MIBC who underwent preoperative neoadjuvant radiotherapy combined with PVBT, followed by postoperative adjuvant radiotherapy and chemotherapy, between January 2018 and December 2020 were included. Tumor response after neoadjuvant radiotherapy, the incidence of PVBT-related complications, and adverse effects of radiotherapy and chemotherapy were assessed. Tumor recurrence and survival outcomes were monitored through outpatient follow-ups and telephone consultations. Risk factors for recurrence were analyzed using statistical methods. Results: A total of 48 patients were included. Four weeks after neoadjuvant radiotherapy, complete response, partial response, stable disease, and disease progression were observed in 3 (6.3%), 23 (47.9%), 20 (41.7%), and 2 (4.2%) patients, respectively. The objective response rate and disease control rate were 54.2% and 95.8%, respectively. Radiation- or chemotherapy-related toxicity occurred in 23 patients (47.9%), all of whom experienced only grade I-II adverse effects, with no grade III-IV toxicity reported. During a follow-up period of 14-58 months, 22 patients (45.83%) experienced recurrence, and 3 patients died due to distant organ metastases. Multi-variate Cox regression analysis identified tumor diameter (≤3.0 cm vs. >3.0 cm) and tumor multiplicity (single vs. multiple) as significant risk factors for recurrence. Conclusions: Preoperative neoadjuvant radiotherapy combined with PVBT, followed by postoperative adjuvant radiotherapy and chemotherapy, is an effective and well-tolerated treatment for T3 MIBC."	bladder
Avelumab maintenance in advanced urothelial carcinoma: real-world data from Northern Spain (AVEBLADDER study).	BACKGROUND: Before the incorporation of enfortumab vedotin with pembrolizumab, the standard of care for patients with locally advanced or metastatic urothelial carcinoma who do not progress after platinum-based chemotherapy was avelumab maintenance therapy, as demonstrated by the JAVELIN 100 trial. However, real-world European data remain scarce. PATIENTS AND METHODS: AVEBLADDER is a retrospective study conducted at 14 hospitals in Northern Spain, including patients with locally advanced or metastatic urothelial carcinoma diagnosed between January 2021 and June 2023. Outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed for patients treated with platinum-based chemotherapy, with and without subsequent avelumab maintenance therapy. non-avelumab patients. Median PFS was 11.33 months (95% CI: 10-13.6) with avelumab and 6.43 months (95% CI: 6-7.6) without. One-year OS probabilities were 81.6% vs. 45.6% (p < 0.001) in the avelumab and non-avelumab groups, respectively. No unexpected toxicities were reported. CONCLUSIONS: Despite proven survival benefits, avelumab uptake in real-world practice is limited by barriers like access, reimbursement, and awareness. These findings align with JAVELIN 100 and underscore the need for further real-world studies to address treatment disparities.	bladder
Prognostic Role of Serum IL-6 Levels in Bladder Cancer Patients and Hints of its Origin.	BACKGROUND: Interleukin-6 (IL-6) is associated with adverse clinical outcome in cancer patients. In bladder cancer (BC) patients, higher IL-6 serum levels have been linked with adverse pathologic features, worse overall survival (OS) and cancer-specific survival (CSS). IL-6 is being investigated as a therapeutic target. However, concentrations in tumor-tissue are not investigated in detail. Objective of this study is to analyze the prognostic value of IL-6 in BC patients and to investigate its concentration in tumor tissue. METHODS: In this single center prospective observational study, preoperative serum samples of 179 BC patients undergoing radical cystectomy were collected between September 2019 and September 2022. Tumor-tissue of additional 20 patients was collected during transurethral resection or radical cystectomy for investigation of IL-6 in tumor tissue supernatant. IL-6 concentration was measured by ELISA. RESULTS: Median serum IL-6 concentration was 5.4 pg/mL. High serum IL-6 was an independent predictor of OS (HR 1.95; 95% CI, 1.07-3.55; P = .03) and CSS (HR 2.31; 95% CI, 1.14-4.68; P = .02) in multivariate Cox regression analyses. Patients with advanced tumor stage, lymph node metastasis, and larger tumor size had significantly higher preoperative serum IL-6 concentration (all P < .01). In tumor tissue supernatant, IL-6 concentration was higher in muscle-invasive BC, with a median of 715.4 pg/mL, as opposed to 20.7 pg/mL in pTa tumor stage (P < .01). CONCLUSIONS: Serum IL-6 is a strong predictor of poor survival rates and adverse pathologic features in BC patients. IL-6 concentrations in tumor tissue supernatant correlate with tumor stage. The role of IL-6 in theranostics of bladder cancer deserves more attention.	bladder
Comparison of microRNA-21 expression in bladder cancer tumor with normal-appearing adjacent tissue and healthy controls.	BACKGROUND: MicroRNAs (miR) regulate post-transcriptional gene expression with an established role in cancer development, angiogenesis, invasion, and metastasis. miR-21 is an oncogenic miR that targets p53 and promotes tumor development. We aim to assess mir-21 expression in bladder cancer (BCa) and compare it to grossly normal-appearing tumor-adjacent tissue and controls. METHODS: This case-control study was implemented from December 2019 to July 2021. We collected 72 specimens of 36 BCa cases (36 specimens of tumoral tissue and 36 specimens of grossly normal-appearing adjacent tissue) and nine specimens from 9 control participants. After total mRNA extraction, microRNA expression was evaluated by Stem-loop real-time RT-PCR. RESULTS: Among the 45 participants, the mean ages in the BCa (36 patients) and control groups (9 patients) were 58.46 ± 16.69 and 56.89 ± 14.92, respectively. The mean expression of miR-21 was 1.8 ± 1.5, 2.8 ± 1.2, and 1.0 ± 0.5 in tumoral tissue, tumor-adjacent grossly normal tissue, and control specimens, respectively. miR-21 expression was higher in tumoral and tumor-adjacent tissues than in controls, with smokers exhibiting significantly elevated levels across all groups (p = 0.037). Additionally, miR-21 expression was significantly higher in high-grade versus low-grade BCa tumors (p = 0.025), with tumoral tissue expression levels of 1.9 ± 1.2 and 1.5 ± 1.3, respectively, and tumor-adjacent tissue levels of 2.7 ± 1.2 and 1.95 ± 1.4, respectively. In the control group, older age was associated with reduced expression of miR-21, whereas in BCa patients, the expression of miR-21 increased with aging (p < 0.05). CONCLUSION: miR-21 expression was higher in the tumor-adjacent tissue than in tumoral tissue and control specimens. The study recognizes certain limitations, such as a limited control group and possible sample loss, which might influence the strength and applicability of the findings.	bladder
Global clinical trial landscape and therapeutic trends in bladder cancer: a systematic analysis.	Bladder cancer (BCa) remains a major oncological challenge worldwide, characterized by high recurrence rate, treatment resistance and variable clinical outcomes. As of 25 April 2025, the assessment of 2899 clinical trials registered in the INFORMA database revealed the main trends affecting this field. Since 2014, the number of BCa trials has increased sharply, and since 2018, it has tended to stabilize. The United States leads the world in research with over 1000 trials. Immunotherapy, especially PD-1/PD-L1 checkpoint blockade and cytotoxic chemotherapy, dominate the treatment field, while targeted therapy has also accelerated its follow-up. Antibody-drug conjugates (ADCs) and Bladder preservation therapy (BPT) have become increasingly prominent, reflecting a shift towards patient-centeredness and individualized and organ-preserving strategies. Driven by regulatory innovation and technological progress, the trial cycle has been accelerated, indicating a transformation in the clinical development process. These findings emphasize the importance of precise oncology and multidisciplinary team management in contemporary BCa treatment paradigms.	bladder
Caspase-1-dependent pyroptosis converts αSMA(+) CAFs into collagen-III(high) iCAFs to fuel chemoresistant cancer stem cells.	The impact of chemotherapy-induced tumor cell pyroptosis on fibroblasts, a key stromal cell type within the tumor microenvironment (TME), remains unexplored. Here, we report morphologically and molecularly distinct subtypes of cancer-associated fibroblasts (CAFs) in bladder cancer, including αSMA(+)IL-6(-) myofibroblastic CAFs (myCAFs), αSMA(-)IL-6(+) inflammatory CAFs (iCAFs), and hybrid i/myCAFs. Caspase-1-dependent tumor pyroptosis releases several inflammatory chemokines, converting αSMA(+) CAF into iCAFs in a CCR6-dependent manner. This is clinically relevant, as a fibroblast gene signature driven by iCAF markers and collagen type III is enriched in patients with chemoresistant bladder cancer after neoadjuvant chemotherapy. Contrary to the current notion, iCAFs, rather than myCAFs, produce collagen III in response to chemotherapy, supporting the expansion of cancer stem cells (CSCs). Thus, tumor cell pyroptosis initiates an iCAF-CSC feedforward loop that drives chemoresistance, indicating that inflammatory cell death is not universally beneficial to anticancer therapy, depending on the target cell type.	bladder
Anti-Cancer Role of Ellagic Acid by Modulating the Altered PI3K/PTEN/Akt Pathway in Bladder Cancer.	Bladder cancer (BCa) is approximately the fourth most prevalent diagnosed cancer in men and is three times less common in women. Therefore, identifying biomarkers, developing more effective therapeutic strategies, and understanding the mechanisms underlying BCa tumor growth and progression are urgently required to improve survival rates. Therefore, we aim to investigate the expression of PTEN/Akt in tissue samples of both non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients (n = 70) and human BCa cell lines T24 and 5637, along with the potent role of ellagic acid (EA) in the modulation of the PTEN/Akt pathway and the resulting therapeutic potential. Results showed low-intensity nuclear or cytoplasmic PTEN staining or loss of PTEN expression in tumor cells and overexpression of p-Akt (Ser-473) with high intensity in the nucleus or cytoplasm. EA treatment of T24 and 5637 cells reduced cell viability, inflammation (NF-κB, COX-2), invasion (MMP-9), induced the caspase (cas-3 and cas-9) cascade signaling pathway, and induced cell apoptosis along with the suppression of the PI3K/PTEN/Akt signaling pathway after 48h in a dose-dependent manner. Thus, these data suggested that the EA showed a strong potential anti-cancer effect in T24 and 5637 cells. In conclusion, the expression of PTEN/p-Akt and the inverse relation indicated an alteration of the PTEN/Akt pathway, and such cases could benefit from treatment with EA in BCa.	bladder
Bladder Cancer Growth is Inhibited by Upregulating CircFUT8 through the METTL14/FMR1 Signaling Pathway.	Bladder cancer (BCa) is one of the most common malignancies worldwide. This study investigates the role of the N(6)-methyladenosine (m6A)/circRNA regulatory axis in BCa tumor growth and elucidates its underlying molecular mechanisms. A total of 15 paired BCa and adjacent non-tumor tissues were collected. CircFUT8 expression was found to be significantly downregulated in BCa tissues and exhibited a positive correlation with methyltransferase-like 14 (METTL14) levels. It could also undergo m6A methylation, its expression was significantly upregulated following METTL14 overexpression in both T24 and UM-UC-3 cells, and silencing circFUT8 counteracted the suppressive effects of METTL14 overexpression on BCa cell growth and migration. RNA immunoprecipitation (RIP) assays confirmed that circFUT8 interacted with fragile X mental retardation 1 (FMR1), and FMR1 overexpression enhanced circFUT8 expression, while FMR1 knockdown diminished the effects of circFUT8 overexpression. In mice, FMR1 overexpression led to elevated circFUT8 levels, reduced Ki67 expression and smaller tumor volumes, and these effects could be reversed following METTL14 knockdown. Collectively, these findings highlight the METTL14/FMR1 signaling axis could enhance circFUT8 expression to inhibit BCa cells growth and migration. CircFUT8 thus represents a promising target for therapeutic intervention and provides novel mechanistic insights into the epigenetic regulation of BCa progression.	bladder
The Spectrum of Polyoma Virus and Polyoma Virus-Like Changes in Urine Cytology: When Should an Atypical Diagnosis Be Considered.	BACKGROUND: While the Paris system for reporting urinary cytology states that cells with well-recognized and typical changes of polyoma virus (PV) infection should not lead to a diagnosis of 'atypia, the prognostic significance of PV-like features is unknown. METHODS: Included were 284 urine cytology cases with PV or PV-like changes. Four cell types were identified. Cell A was typical of PV infection, cell B had a spider-web chromatin pattern, and cells C and D were degenerated cells with clumpy chromatin or homogeneous severely hyperchromatic nuclei, respectively. Events were correlated with a subsequent histological diagnosis of high-grade urothelial carcinoma (HGUC). RESULTS: 47% of cases had more than one cell type. The most common cell was D (64%) and the least common was A (27%). The most common cell to be present in isolation was D (n = 109, 60%). 92% of cases with cell A had other cell types. Overall, the presence of cell A was associated with a benign follow-up (1.2% association with HGUC). There was a gradual increase in the association with a HGUC diagnosis in cases with cells B (PPV = 8%), C (PPV = 15.5%), and D (PPV = 44%). The presence of only cells B, C, or D was predictive of HGUC in 22.4%, 33.3%, and 61.5%, respectively. CONCLUSIONS: Cases with cell type A can be confidently diagnosed as 'negative for HGUC', even in the presence of associated cells with PV-like changes. Cases with cells displaying PV-like features (cell type B, C, or D) in the absence of type A features may represent degenerated HGUC cells.	bladder